№ 6 / 2015 / 37-44

Induction of redox-sensitive Keap1/Nrf2/ARE system alters classical activation of macrophages

Author: Kozhin P.M.¹, Zenkov N.K.², Lemza A.E.³, Chechushkov A.V.⁴, Zaitseva N.S.⁵, Kandalintseva N.V.⁶, Menshchikova E.B.⁷

Author Affiliations

Abstract

The aim of the study was to investigate the effect of phenolic antioxidant 3-(3’-tert-butyl-4’-hydroxyphenyl)propyl thiosulfonate sodium (TS-13), which induces redox-sensitive Keap1/Nrf2/ARE system, on classical polarization of macrophages. The influence of TS-13 on expression of costimulatory molecule CD86 and nitric oxide (NO^·) production by peritoneal macrophages of BALB/c mice has been studied. TS-13 has been found to inhibit surface antigen CD86 expression in the absence of additional priming with IFNγ and LPS, as well as in low concentrations in the presence of IFNγ and LPS. High concentrations (100 μM) of TC-13 have a synergistic effect with inducers of classical activation and bacterial agents (BCG) and increase expression of costimulatory molecules. Further, TS-13 dose-dependently stimulates the production of NO^· by macrophages, regardless of the additional stimulation of IFNγ + LPS or BCG. The data suggest that the induction of Keap1/Nrf2/ARE system, which activates the defense mechanisms against aggressive influences (including changes in redox status), can both inhibit and enhance macrophage activation by the classical pathway.

Key words

CD86, TS-13, nitric oxide, macrophage polarization, Keap1/Nrf2/ARE signal system

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About Authors (Correspondence):

Kozhin P.M. – researcher, laboratory of molecular mechanisms of free radical processes, e-mail: kozhinpm@gmail.com

Zenkov N.K. – doctor of biological sciences, leading researcher, laboratory of molecular mechanisms of free radical processes, e-mail: lemen@centercem.ru

Lemza A.E. – candidate of biological sciences, researcher, laboratory of molecular mechanisms of free radical processes, e-mail: lemza.ae@yandex.ru

Chechushkov A.V. – researcher, laboratory of molecular mechanisms of free radical processes, e-mail: achechushkov@gmail.com

Zaitseva N.S. – candidate of biological sciences, researcher, laboratory of molecular mechanisms of free radical processes, e-mail: nszaitseva@gmail.com

Kandalintseva N.V. – candidate of chemical sciences, director of Institute of Natural, Social and Economic Sciences, e-mail: aquaphenol@mail.ru

Menshchikova E.B. – doctor of medical sciences, head of the laboratory of molecular mechanisms of free radical processes, e-mail: lemen@centercem.ru

Full Text

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Received: 12/01/2016